Background: There is increasing experimental evidence that hypoxia induces inflammationin the gastrointestinal tract. Hypoxia-inducible transcription factor (HIF)-1α influencesadaptive immunity and has been shown to induce barrier-protective genes in the case ofexperimentally-induced colitis. The clinical impact of hypoxia in patients with inflammatorybowel disease (IBD) is so far poorly investigated. Aim: We wanted to evaluate if flights andjourneys to regions ≥2000 meter above sea level are associated with the occurrence of flaresin IBD patients in the following 4 weeks. Methods: A questionnaire was completed byinpatients and outpatients of the IBD clinics of three tertiary referral centers presenting withan IBD flare in the period from Sept 1st 2009 to August 31st 2010. Patients were inquiredabout their habits in the 4 weeks prior to the flare. Patients with flares were matched withan IBD group in remission during the observation period (according to age, gender, smokinghabits, and medication). Results: A total of 103 IBD patients were included (43 Crohn'sdisease (CD), whereof 65% female, 60 ulcerative colitis, whereof 47% female, mean age39.3±14.6 years for CD and 43.1±14.2 years for UC). Fifty-two patients with flares werematched to 51 patients without flare. Overall, IBD-patients with flares had significantly morefrequently a flight and/or journey to regions ≥ 2000 meters above sea level in the observationperiod compared to the patients in remission (21/52 (40.4%) vs. 8/51 (15.7%), p=0.005).There was a statistically significant correlation between the occurrence of a flare and a flightand/or journey to regions ≥ 2000 meters above sea level among CD patients with flares ascompared to CD patients in remission (8/21 (38.1%) vs. 2/22 (9.1%), p=0.024). A trendfor more frequent flights and high-altitude journeys was observed in UC patients with flares(13/31 (41.9%) vs. 6/29 (20.7%), p=0.077). Mean flight duration was 5.8±4.3 hours. Thegroups were controlled for the following factors (always flare group cited first): age (39.6±13.4vs. 43.5±14.6, p=0.102), smoking (16/52 vs. 10/51, p=0.120), regular sports activities (32/52 vs. 33/51, p=0.739), treatment with antibiotics in the 4 weeks before flare (8/52 vs. 7/51, p=0.811), NSAID intake (12/52 vs. 7/51, p=0.221), frequency of chronic obstructivepulmonary disease (both groups 0) and oxygen therapy (both groups 0). Conclusion: IBDpatients with a flare had significantly more frequent flights and/or high-altitude journeyswithin four weeks prior to the IBD flare compared to the group that was in remission. Weconclude that flights and stays in high altitude are a risk factor for IBD flares.